Observations in this laboratory have led us to hypothesize that the predisposition of NZB and other autoimmune-lymphoproliferative mouse strains (MRL/1pr, MRL/ plus plus, BXSB, and PN) may derive in part from an abnormality in the steady-state kinetics of the pluripotential hemopoietic stem cell population. An augmented cycling to resting cell ration may generate increased numbers of target cells at risk for autoimmune expression and neoplastic transformation. Our proposed work will characterize the preautoimmune stem cell compartment in these mice; its total population and cycling fractions in hemopoietic tissues at different ages, employing endogenous and transplantation assays. We will determine possible abnormalities in the capacity of NZB stem cells to respond to feedback signals or to produce such signals in in vivo double diffusion chamber experiments. Transplantability and prevention of the disorders of these strains and the role of the thymus in modulating resultant hemopoiesis will be assessed. The kinetics of stem cell regeneration and differentiation and differentiation in lethally-irradiated hosts will be studied. The effects of environmental factors such as diet and sex hormones on stem cell activity will also be examined.